Preparation of beta-alanine



v dihydracrylic. acid,

examples.

Patented Feb. 25, 1 947 UNITED v STATE 5 *PATENT QFFICE.

PREPARATIONOF BETA-ALANINEY v 1 Philip M. Kirk, Stamford, Conn, assignor to I American Cyanamid Company,

N. Y., a corporation of Maine New York,

No Drawing. Application June 25, 1942,

Serial No. 448,489

8 Claims. 1

This invention relates to the preparation of beta-aminopropionic acid (beta-alanine) and more particularly to the preparation of betaaminopropionic acid in one step from iminodipropionic acid or dihydr'acrylic acid and ammonium hydroxide.

According to the present invention I have found that either iminodipropionic acid,

- CHzCH2CO OH CHzCHaCOOH oraomcoon or thiodihydracrylic acid,

OHzOHzCOOH CHzCHzC OOH when. heated with ammonium hydroxide in a pressure vessel at temperatures ranging from about 180 C. to about 225 C. for from about one to abouttwenty-four hours, react to produce beta-aminopropionic acid. If desired, a small amount of a corrosion and oxidation inhibitor such as, for example, diphenylamine, may be added to the reaction mixture.

Beta-aminopropionic acid has recently become an important intermediate in the preparation of pantothenic acid, and accordingly, a commercially practicable method of preparing this intermediate is indicated. The process of the present invention provides such a method.

' Itis an advantage of the'present invention that the only reactants essential for the operation of the process are iminodipropionic acid, dlhydracrylic acid, or thiodihydracrylic acid and ammonium hydroxide. The ammonium hydroxide is, of course, readily'avallable and cheap; iminodipropionic acid, dihydracrylic acid, and thiodihydracrylic acid are not disproportionately expensive and are readily available.

It; is another advantage of the present invention that the reaction involved is simple, easily controlled, and takes place in a single step. Thus,

'beta-aminopropionic acid may be produced di- 'rectly from iminodipropionic acid, dihydracrylic acid, or thiodihydracrylic acid without requiring the isolation of any intermediate product.

It is a further advantage of the invention that the beta-aminopropionic acid is obtainedin good yield in'a form which permits easy separation from the. reaction mixture.

The invention will be described in greater detail in conjunction with the following specific It should be understood that these examples are merely specific embodiments of the invention and it is not intended to limit the scope of the invention to the specific details therein set forth. Parts are by weight unless otherwise stated.

7 Example 1 193 parts (1.20 mols) of iminodipropionic acid, 600 parts of 28% ammonium hydroxide, 1080 parts of water, and 2 parts of diphenylamine were heated togetherin an autoclave for four hours at 200 C. The solution was filtered, treated with decolorizing carbon at 70 0., again filtered, and

the filtrate evaporated to'a thick syrup.. The syrup was then diluted with about 500 mls. ,of

methanol, whereupon parts of beta-aminopropionic acid suitablefor the production ,of pantothenic acid without further purification crystallized, out. Yield: 30.4%. 1 W Example 2 e After recovery of the beta-aminopropionicacid as described in Example 1, the filtratewas evaporated to reclaim the methanol. The resulting syrupy residue was heated with an additional amount of ammonium hydroxide at200 C.'= ,for

heated together in an autoclave for four hours at 200 C. Th solution was filtered, treated with decolorizing carbon at (3., again filtered, and the filtrate evaporated to a thick syrup. The syrup was then dilute with about 500 mls. of methanol, whereupon 31.7 parts of beta-aminopropionic acid crystallized out. Yield: 29.7%.

Example 4 After recovery of the beta-aminopropionic acid as described in Example 3, the filtrate was evaporated to reclaim the methanol. The resulting syrupy residue was heated with an additional amount of ammonium hydroxide at 200. C. for

four hours and the solution treated as described in Example 3. A similar further yield of betaaminopropionic acid crystals was obtained Eample'5 g 200 parts of thiodihydracrylic acid, 526 parts of 28% ammonium hydroxide, and 702 parts of water were heated in an autoclave at about 200 C. for four and a half hours. The solution was cooled, clarified, anad concentrated to small volume under reduced pressure. 1 l. of dry methanol was added, the mixture was stirred and then cooled, whereupon beta-aminopropionic acid crystallized out. Yield about 28%.

1 varied within wide limits.

2,41e,oso

Example 6 syrupy residue was heated with an additional amount of ammonium hydroxide at 200 C. for four hours and the solution treated as described in Example 5. A similar further yield of betaaminopropionic acid crystals was obtained.

Apparently an equilibrium is reached in the '1 reaction between iminodipropionic acid, dihydracrylic acid, or thiodihydracrylic acid and ammonium hydroxide which may account for the fact that the residue from one operation may be used as the reactant in another with no appreciable decrease in the yield of beta-aminopro- -pionic acid obtained. When over-all yields are considered, this feature of my process is extremely important since yields approaching the theoretical may be obtained by re-working the residues.

Further evidence for the existence of an equilibrium mixture was obtained from a series of 1 further reactions wherein concentrations of the reactants, time of heating .and temperature-were The strength of the ammoniumhydroxide was varied from 2% to 28% with similar variations in the proportions j of iminodipropionic acid, dihydracrylic acid, and thiodihydracrylic acid basedon the proportion of ammonia; the time of heating, from one to twenty-four hours; and the temperature, from 150 to 250 C. In all cases beta-aminopropionic acid was obtained but only drastic changes in the 1 concentration of reactants gave more than a 35% yield. For example, very low concentrations of iminodipropionic acid and dihydracrylic acid pro- 1 duced beta-aminoproprionic acid in yields of the 1 order of 50%60% but the increased cost of re- 1 moving the larger volumes of solvent present would probably neutralize the economical advantages resulting from the increased yields.

The beta-aminopropionic acid produced by my I proces may, if desired, be converted to an acid salt such as the hydrochloride or to a salt of a metal such as an alkali or alkaline earth metal, and isloated in this form. I prefer, however, to isolate the beta-'aminopropionic acid directly from the concentrated syrupy reaction product by diluting it with absolute methanol. When so isolated, the beta-aminopropionic acid is in a pur form and may then, if desired, be converted to the salts when they are required as intermediates in processes for producing pantothenic acid.

Methanol appears to be peculiarly suited for the above isolation or crystallization step. Attempts to dilute with various other aliphatic alcohols such as ethanol or propanol have been unsatisfactory.

In the reaction between iminodipropionic acid, dihydracrylic acid, or thiodihydracrylic acid and ammonium hydroxide under the conditions described above, it may be desirable in some instances to add other substances to the reaction mixture.

For example, dehydration catalysts, ammonium salts of weak acids such as ammonium carbonate, inhibitors, anti-oxidants, and other suitable reagents for slightly altering the 1 course of speed of the reaction may be added.

I claim: 1. The process of producing lceta-aminopropionic acid which comprises reacting a. member of the group consisting of iminodipropionic acid, dihydracrylic acid, and thiodihydracrylic acid with aqueous ammonia at an elevated temperature.

' pionic acid which comprises heating iminodipropionic acid and aqueous ammonia at a temperature of about 200 C. for about four hours.

5. The process of producing beta-aminopropionic acid which comprises heating dihydracrylic acid and aqueous ammonia at a temperature of about 200 C. for about four hours.

6. The process of producing beta-aminopropionic acid which comprises heating thiodihydracrylic acid and aqueous ammonia at a temperature of about 200 C. for about four hours.

7. The process of producing beta-aminopropionic acid which comprises reacting a member of the group consisting of iminodipropionic acid, dihydracrylic acid,- and thiodihydracrylic acid with aqueous ammonia at a temperature of from about 180 C. to about 225 C.'for from about one to about twenty-four hours, concentrating the reaction mixture to a syrup, and diluting the syrup with methanol to cause precipitation of beta-aminopropionic acid.

8. The process of producing beta-aminopropionic acid which comprises reacting a member of the group consisting of iminodipropionic acid, dihydracrylic acid, and thiodihydracrylic 'acid with aqueous ammonia at a temperature of from about 180 C. to about 225 C. for from about twenty-four hours, concentrating the reaction mixture to a syrup, diluting the syrup with methanol, collecting the precipitated beta-aminopropionic acid, concentrating the residue, and reacting said residue with aqueous ammonia at a temperature of from about 180 C. to about 225" C. for from about one to about twenty-four hours to produce a further quantity of beta-aminopropionic acid.

PHILIP M. KIRK.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Toennies Nov. 26, 1940 

